3D Printed Hydrogels with Aligned Microchannels to Guide Neural Stem Cell Migration.
3D Printed Hydrogels with Aligned Microchannels to Guide Neural Stem Cell Migration.
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DOI：
10.1021/acsbiomaterials.0c01619
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发表时间：
2021-01
影响因子：
5.8
通讯作者：
Cui Li;Mitchell A. Kuss;Yunfan Kong;F. Nie;Xiaoyan Liu;Bo Liu;A. Dunaevsky;P. Fayad;B. Duan;Xiaowei Li
中科院分区：
文献类型：
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作者：
Cui Li;Mitchell A. Kuss;Yunfan Kong;F. Nie;Xiaoyan Liu;Bo Liu;A. Dunaevsky;P. Fayad;B. Duan;Xiaowei Li
创伤性或缺血性脑损伤后，细胞快速死亡和细胞外基质降解导致脑损伤部位形成空腔，这是导致长期神经功能缺损和永久残疾的原因。神经干/祖细胞（NSCs）移植是重建病变腔和促进组织再生的一种有前途的策略。特别是，促进移植的神经干细胞的神经元迁移、组织和整合对于基于干细胞的治疗的成功至关重要。这对大脑皮层尤其重要，大脑皮层是脑损伤中最常见的区域，因为大脑皮层的高度组织结构对其功能至关重要。基于生物材料的策略显示出调节病变部位微环境以支持移植的干细胞的一些前景，但在证明有组织的细胞植入和整合到大脑中方面的进展非常有限。尚未制定出充分应对这些挑战的有效办法。在这里，我们实现了一种基于数字光处理的3D打印机，并打印出具有设计形状、单轴对齐微通道和可调机械性能的水凝胶支架。我们证明了能够实现高形状精度的病变部位与脑组织匹配的机械性能。我们还建立了3D打印水凝胶支架内生物活性分子分布的空间控制。这些打印的水凝胶支架显示出高的神经相容性，其具有沿着微通道沿着的神经元生长。这项研究将提供一种基于生物材料的方法，可以作为移植的NSC组织和整合损伤后脑组织再生的保护和指导工具。
Following traumatic or ischemic brain injury, rapid cell death and extracellular matrix degradation lead to the formation of a cavity at the brain lesion site, which is responsible for prolonged neurological deficits and permanent disability. Transplantation of neural stem/progenitor cells (NSCs) represents a promising strategy for reconstructing the lesion cavity and promoting tissue regeneration. In particular, the promotion of neuronal migration, organization, and integration of transplanted NSCs is critical to the success of stem cell-based therapy. This is particularly important for the cerebral cortex, the most common area involved in brain injuries, because the highly organized structure of the cerebral cortex is essential to its function. Biomaterials-based strategies show some promise for conditioning the lesion site microenvironment to support transplanted stem cells, but the progress in demonstrating organized cell engraftment and integration into the brain is very limited. An effective approach to sufficiently address these challenges has not yet been developed. Here, we have implemented a digital light-processing-based 3D printer and printed hydrogel scaffolds with a designed shape, uniaxially aligned microchannels, and tunable mechanical properties. We demonstrated the capacity to achieve high shape precision to the lesion site with brain tissue-matching mechanical properties. We also established spatial control of bioactive molecule distribution within 3D printed hydrogel scaffolds. These printed hydrogel scaffolds have shown high neuro-compatibility with aligned neuronal outgrowth along with the microchannels. This study will provide a biomaterial-based approach that can serve as a protective and guidance vehicle for transplanted NSC organization and integration for brain tissue regeneration after injuries.